Bipolar disorder (BD) is a serious and chronic mental illness that is associated with substantial impairment in quality of life and functional outcomes, high rates of suicide, and high financial costs. In spite of a proliferation of treatments for BD, nearly half of individuals with BD do not benefit from pharmacotherapy because of sub-optimal medication treatment adherence. Non-adherence with BD medication treatment dramatically worsens outcomes. Reasons for non-adherence among individuals with BD are multi-dimensional, and it has been suggested that adherence enhancement might work best if the intervention specifically addresses factors that are important and modifiable for a specific individual. In spite of the enormity of the problem, the literature on interventions to improve treatment adherence is surprisingly limited. There is an urgent need for interventions to enhance treatment adherence among BD patients that: 1) are at high risk for future treatment non-adherence; 2) may not have access to or interest in long-term, high-intensity, and specialized care; and 3) are flexible and patient-focused taking into account reasons for non-adherence for a specific individual. The proposed study builds upon the investigator's extensive body of work in BD treatment adherence, and development of a customized adherence enhancement (CAE) psychosocial approach that is brief, efficient, and practical. The investigators have manualized the CAE intervention for intended use by staff that might typically be present in public-sector mental health settings. Pilot work by these investigators suggests that CAE can improve medication treatment adherence, reduce BD symptoms and improve functional status in poorly adherent BD patients. These preliminary findings have set the stage for the next appropriate step, which is testing of the CAE intervention compared to broadly-directed, non-individualized education (EDU) in a prospective, randomized controlled trial (RCT). The proposed study is a first-ever RCT focused specifically on BD treatment adherence enhancement, and will test whether CAE improves adherence and mental health outcomes compared to EDU. A unique feature of the proposed study is a supplemental and complementary qualitative evaluation that will inform future intervention refinements. Taken together, the proposed project has the potential to greatly advance the care of BD patients who are at greatest risk for poor health outcomes, with findings expected to be generalizable across a variety of treatment settings. PUBLIC HEALTH RELEVANCE: The proposal will test a brief, tailored intervention intended to improve medication treatment adherence in high-risk patients with bipolar disorder. Given the enormous personal and societal burden of non-adherence on patients and families, the proposal has substantial public health implications.